| glutamate transporter reverse transport inhibition prodrug excitotoxicity electrophysiology

Most of molecules enter or leave cells mainly via membrane transport proteins, which play important roles in several cellular functions, including cell metabolism, ion homeostasis, signal transduction, the recognition process in the immune system, energy transduction, etc. There are three major types of transport proteins, ATP-powered pumps, channel proteins and transporters. Transport proteins such as channels and transporters play important roles in the maintenance of intracellular homeostasis, and mutations in these transport protein genes have been identified in the pathogenesis of a number of hereditary diseases. In the central nervous system, ion channels have been linked to, but not limited to, many diseases such asataxias, paralyses, epilepsies, and deafness. This indicates the roles of ion channels in the initiation and coordination of movement, sensory perception, and encoding and processing of information. Ion channels are a major class of drug targets in drug development.

MCE designs a unique collection of 1,852 smal-molecule modulators that can be used for the research of Ion Channel and Membrane Transporter or high throughput screening (HTS) related drug discovery.

On May 15, 2024, "Dimerization and antidepressant recognition at noradrenaline transporter" was published online by Nature. The research findings were an effort from Shanghai Institute of Materia Medica, Chinese Academy of Sciences. This study unraveled the important neural system target - the noradrenaline transporter (NET), obtaining the binding modes of human NET homodimers with the natural substrate norepinephrine (NE) and six selective antidepressants. It laid an important theoretical foundation for understanding the physiological regulation mechanisms of NET and other monoamine transporters.

The Norepinephrine Transporter (NET) Compound Library is obtained by computer-aided virtual screening based on the HY-L901 compound library . The specific screening process includes molecular docking screening, key pharmacophore screening, and CNS-MPO screening, which can be used for new drug discovery targeting the noradrenaline transporter.

Glutamine is an important metabolic fuel that helps rapidly proliferating cells meet the increased demand for ATP, biosynthetic precursors, and reducing agents. Glutamine Metabolism pathway involves the initial deamination of glutamine by glutaminase(GLS), yielding glutamate and ammonia. Glutamate is converted to the TCA cycle intermediate α-ketoglutarate (α-KG) by either glutamate dehydrogenase (GDH) or by the alanine or aspartate transaminases (TAs), to produce both ATP and anabolic carbons for the synthesis of amino acids, nucleotides and lipids. During periods of hypoxia or mitochondrial dysfunction, α-KG can be converted to citrate in a reductive carboxylation reaction catalyzed by IDH2. The newly formed citrate exits the mitochondria where it is used to synthesize fatty acids and amino acids and produce the reducing agent, NADPH.

Cancer cells display an altered metabolic circuitry that is directly regulated by oncogenic mutations and loss of tumor suppressors. Mounting evidence indicates that altered glutamine metabolism in cancer cells has critical roles in supporting macromolecule biosynthesis, regulating signaling pathways, and maintaining redox homeostasis, all of which contribute to cancer cell proliferation and survival. Thus, intervention in glutamine metabolic processes could provide novel approaches to improve cancer treatment.

MCE owns a unique collection of 1,326 compounds targeting the mainly proteins and enzymes involved in glutamine metabolism pathway. Glutamine Metabolism compound library is a useful tool for intervention in glutamine metabolic processes.

MCE 5K Scaffold Library consists of 5,000 lead-like compounds. Each compound represents one unique scaffold. All compounds are compatible with Lipinski’s rule (Rule of 5) with multiple characteristics such as calculated good solubility (-3.2 < logP < 5), oral bioavailability (RotB <= 10), drug transportability (PSA < 120). Compounds contained within the library have been screened to remove any inappropriate chemical structures, avoiding “false hits”. The sufficient diverse of compound structure makes this library a powerful tool for drug screening.

Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels which include coronary heart disease, cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, etc. CVDs are the number 1 cause of death globally. Smoking, unhealthy nutrition, aging population, lack of physical activity, arterial hypertension, or diabetes can promote cardiovascular disease like myocardial infarction or stroke. It is multifactorial and encompasses a multitude of mechanisms, such as eNOS uncoupling, reactive oxygen species formation, chronic inflammatory disorders and abnormal calcium homeostasis. Antioxidant, anti-inflammatory and anti-diabetes agents may reduce the cardiovascular disease risk.

MCE supplies a unique collection of 1,990 compounds with confirmed anti-cardiovascular activity. These compounds mainly target metabolic enzyme, membrane transporter, ion channel, inflammation related signaling pathways. MCE Anti-Cardiovascular Disease Compound Library can be used for cardiovascular diseases related research and high throughput and high content screening for new drugs.

MCE 50K Diversity Library consists of 50,000 lead-like compounds with multiple characteristics such as calculated good solubility (-3.2 < logP < 5), oral bioavailability (RotB <= 10), drug transportability (PSA < 120). These compounds were selected by dissimilarity search with an average Tanimoto Coefficient of 0.52. There are 36,857 unique scaffolds and each scaffold 1 to 7 compounds. What’s more, compounds with the same scaffold have as many functional groups as possible, which make abundant chemical spaces. This exceptionally diverse library is highly recommended for random screening against new as well as popular targets based its novel, diverse scaffolds, abundant chemical spaces and the convenience for subsequent modification.

Viruses are much simpler organisms than bacteria, and they are made from protein substances and nucleic acid. Despite the fact that the exact mechanism of infection is extremely specific to each type of virus, the general scheme of infection can be represented in the following manner: A virus is absorbed at the surface of a host cell and then permeates through the membrane, where it releases nucleic acid from its protein protection. Then the viral nucleic acid begins to replicate, and transcription of the viral genome takes place either in the cytoplasm, or in the nucleus of the host cell. As a result of these events, a large amount of viral nucleic acid and protein are made to make new generations of virions. Therefore, one mechanism of action of antiviral drugs is to interfere with the ability of a virus to get into a target cell. A second mechanism of action is to target the processes that synthesize virus components after a virus invades a cell, such as nucleotide or nucleoside analogs.

MCE designs a unique collection of 1,435 anti-virus compounds that target several viruses, including SARS-CoV, HBV, HCV, HIV, HSV and Influenza Virus. It’s an effective tool for anti-virus drug discovery.

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE Lead-like Covalent Screening Library offers a valuable resource of 1,049 lead-like compounds with commonly used covalent warheads. These warheads, such as acrylamide, activated terminal alkyne, acyloxymethyl ketone, and boronic acid, are capable of reacting with specific amino acid residues, including cysteine, lysine, serine, and histidine. The inclusion of these reactive warheads in the library allows researchers to explore the potential of covalent inhibition, a powerful approach in drug discovery.

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE covalent inhibitor library contains 5,810 small molecules including identified covalent inhibitors and other molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

MCE Covalent inhibitor Library plus, with more powerful screening capability, further complement Covalent inhibitor Library (HY-L036) by adding some fragment compounds with covalent warheads.

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE covalent inhibitor library contains 1,458 small molecules including identified covalent inhibitors and other bioactive molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, Sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

Methylation is an epigenetic modification mechanism that involves adding methyl groups to molecules such as DNA and histones, which can alter gene expression without changing the DNA sequence. This process is catalyzed by enzymes such as DNA methyltransferases (DNMTs) and histone methyltransferases (HMTs), and can be reversed by demethylases. The balance of methylation and demethylation is crucial for maintaining cellular function and genomic stability. Abnormal regulation of methylation may lead to a variety of diseases, including cancer, neurological disorders, and developmental abnormalities. A deep understanding of the molecular mechanisms of methylation metabolism is essential for developing therapeutic strategies for diseases associated with methylation dysregulation.

MCE contains 309 compounds targeting methylation/demethylation enzymes, which is of significant value for studying the pathways of methylation metabolism and exploring their mechanisms of action in diseases.

Nucleoside and nucleotide analogues are synthetic, chemically modified compounds that have been developed to mimic their physiological counterparts in order to exploit cellular metabolism and subsequently be incorporated into DNA and RNA to inhibit cellular division and viral replication. In addition to their incorporation into nucleic acids, nucleoside and nucleotide analogues can interact with and inhibit essential enzymes such as human and viral polymerases (that is, DNA-dependent DNA polymerases, RNA-dependent DNA polymerases or RNA-dependent RNA polymerases), kinases, ribonucleotide reductase, DNA methyltransferases, purine and pyrimidine nucleoside phosphorylase and thymidylate synthase. These actions of nucleoside and nucleotide analogues have potential therapeutic benefits — for example, in the inhibition of cancer cell growth, the inhibition of viral replication as well as other indications.

MCE offers a unique collection of 578 nucleotide compounds including nucleotide, nucleoside and their structural analogues. MCE Nucleotide Compound Library is a useful tool to discover anti-cancer and antiviral drugs for high throughput screening (HTS) and high content screening (HCS).

A diverse compound library with favorable ADMET properties (Absorption, Distribution, Metabolism, Excretion, and Toxicity) is crucial in drug discovery. Early evaluation of ADMET properties allows for the exclusion of molecules with unfavorable profiles at the initial stages, thereby reducing the risk of late-stage development failures, lowering R&D costs, and accelerating optimization of lead compounds. Based on predictions from ADMET-related AI algorithms, the compounds in this library are predicted to exhibit favorable oral bioavailability (F > 30%), reasonable plasma protein binding (PPB < 98%), minimized CYP3A4 inhibition potential (inhibition probability < 50%, CYP3A4 is the most critical drug-metabolizing enzyme in the cytochrome P450 family) , low toxicity profiles, with 140 potentially toxic substructures pre-identified and excluded via substructure searching to eliminate compounds containing hazardous fragments. The diversity library enables broad applicability in high-throughput screening (HTS) and high-content screening (HCS).

Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. A variety of HF-1 target genes have been identified thus far which encode proteins that play key roles in critical developmental and physiological processes including angiogenesis/vascular remodeling, erythropoiesis, glucose transport, glycolysis, iron transport, and cell proliferation/survival.

HIF-1 is a heterodimeric transcription factor consisting of a constitutively expressed β-subunit and an oxygen-regulated α-subunit. The unique feature of HIF-1 is the regulation of HIF-1α expression and activity based upon the cellular O₂ concentration. Under normoxic conditions, hydroxylation of HIF-1α on these different proline residues is essential for HIF proteolytic degradation by promoting interaction with the von Hippel-Lindau tumor-suppressor protein (pVHL) through hydrogen bonding to the hydroxyproline-binding pocket in the pVHL β-domain. As oxygen levels decrease, hydroxylation of HIF decreases; HIF-1α then no longer binds pVHL, and becomes stabilized, allowing more of the protein to translocate to the cell’s nucleus, where it acts as a transcription factor, upregulating (often within minutes) the production of proteins that stimulate blood perfusion in tissues and thus tissue oxygenation.

MCE offers a unique collection of 3,311 oxygen sensing related compounds targeting HIF/HIF Prolyl-Hydroxylase, MAPK/ERK, PI3K/AKT signaling pathways, etc. MCE Oxygen Sensing Compound Library is a useful tool to study hypoxia, oxidative stress and discover new anti-cancer drugs.

Hormones are a class of biologically active substances secreted by endocrine gland cells, which are transported through the circulatory system to various parts of the body, and precisely act on specific target organs or cells, playing a crucial role in regulating the growth, development, metabolism, and reproduction of organisms. The mechanisms of hormone action are diverse and complex. Some hormones (such as corticosteroids, vitamin D, and thyroid hormones) can enter the cell interior and interact with receptors in the nucleus, thereby regulating gene expression and affecting cell function. Other hormones (such as growth hormone and thyrotropin-releasing hormone) bind directly to receptors on the cell surface, exerting their effects by regulating enzyme activity or influencing the state of ion channels. Additionally, hormones play a key role in the study of endocrine and metabolic diseases, and are closely related to the development of diseases such as diabetes and thyroid diseases.

MCE has included 87 human hormone compounds, which is of great significance for the study of human metabolic pathways, and can also be used to build a metabonomics database.

Neurodegenerative diseases are characterised by progressive dysfunction and death of neurons, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis (MS). Neuroprotection is an approach to preserve neurons so that neurons cannot be hurt by different pathological factors in neurodegenerative diseases. Neuroprotectors are some agonists and antagonists targeting some key targets in neuroprotactive signal pathways, such as calcium and sodium channel blockers, GABA receptor agonists, NMDA receptor Antagonists, etc. Current neuroprotectors cannot reverse existing damage, but they may protect against further nerve damage and slow down any degeneration of the central nervous system (CNS) and still play important roles in the treatment of neurodegenerative diseases.

MCE offers a unique collection of 1,471 compounds with potential neuroprotective activities. These compounds mainly act on some key targets in neuroprotetive signal pathways, such as calcium channel, sodium channel, adenosine A1 receptor, etc. MCE Neuroprotective Compopund Library is a useful tool in neuroprotective drug discovery.

Bile acids are a class of amphiphilic molecules derived from the metabolic breakdown of cholesterol, primarily synthesized in the liver, and play a crucial role in the intestines. Based on their structural characteristics, bile acids are mainly divided into two categories: free bile acids (including Cholic acid, Deoxycholic acid, Chenodeoxycholic acid) and conjugated bile acids (including Glycocholic acid, Glycochenodeoxycholic acid, Taurocholic acid, etc.). Bile acids play a significant role in the pathophysiological research of liver and gastrointestinal diseases and are closely associated with the occurrence of metabolic diseases such as obesity, type II diabetes, non-alcoholic fatty liver disease, and atherosclerosis. Bile acids maintain metabolic balance within the body by regulating sugar metabolism, lipid metabolism, and amino acid metabolism, and they influence the activity of metabolism-related enzymes and transporters. In addition, Bile acids can also be used to construct a bile acid metabolism research platform, which helps to delve into the metabolic pathways and dynamic changes of bile acids in living organisms and aids in identifying new biomarkers for certain diseases.

MCE included 60 bile acids, including Cholic acid, Deoxycholic acid, Glycocholic acid, etc., which are effective tools for the study of liver and gallbladder diseases.

Natural products are an attractive source with varied structures that exhibit potent biological activities, and desirable pharmacological profiles. The core scaffold of a natural product can also provide a biologically validated framework upon which to display diverse functional groups. Inspired by bioactive natural products, natural product-like compounds, occupying the same chemical space, are ideally suited to explore and to facilitate understanding of biological pathways.

MCE 10K Natural Product-like Compound Library consists of 10,000 natural product-like compounds. Each compound has scaffold of natural products or Tanimoto coefficient >0.6 with natural products. The natural-likeness scoring of these compounds is >-2. What’s more, compounds in the library are drug-like and readily available for re-supply, making it a powerful tool for new drug research and development. It can be widely applied in high-throughput screening (HTS) and high-content screening (HCS).

Natural products are an attractive source with varied structures that exhibit potent biological activities, and desirable pharmacological profiles. The core scaffold of a natural product can also provide a biologically validated framework upon which to display diverse functional groups. Inspired by bioactive natural products, natural product-like compounds, occupying the same chemical space, are ideally suited to explore and to facilitate understanding of biological pathways.

MCE 5K Natural Product-like Compound Library consists of 5,000 natural product-like compounds. Each compound has scaffold of natural products or Tanimoto coefficient >0.6 with natural products. The natural-likeness scoring of these compounds is >-2. What’s more, compounds in the library are drug-like and readily available for re-supply, making it a powerful tool for new drug research and development. It can be widely applied in high-throughput screening (HTS) and high-content screening (HCS).

Mutations in oncogenes and tumor suppressor genes can modify multiple signaling pathways and in turn cell metabolism, which facilitates tumorigenesis. The paramount hallmark of tumor metabolism is “aerobic glycolysis” or the Warburg effect, coined by Otto Warburg in 1926, in which cancer cells produce most of energy from glycolysis pathway regardless of whether in aerobic or anaerobic condition. Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside. The increased uptake of glucose is facilitated by the overexpression of several isoforms of membrane glucose transporters (GLUTs). Likewise, the metabolic pathways of glutamine, amino acid and fat metabolism are also altered. Recent trends in anti-cancer drug discovery suggests that targeting the altered metabolic pathways of cancer cells result in energy crisis inside the cancer cells and can selectively inhibit cancer cell proliferation by delaying or suppressing tumor growth.

MCE provides a unique collection of 2,890 compounds which cover various tumor metabolism-related signaling pathways. These compounds can be used for anti-cancer metabolism targets identification, validation as well anti-cancer drug discovery.

Non-steroidal anti-inflammatory drugs (NSAIDs) are members of a therapeutic drug class with potent anti-inflammatory, analgesic and antipyretic activity, and are among the most widely used drugs worldwide. The most prominent NSAIDs are aspirin, ibuprofen, and naproxen.

The main mechanism of action of NSAIDs is the inhibition of the enzyme cyclooxygenase (COX), based on which NSAIDs can be classified into two types: non-selective and COX-2 selective. Most NSAIDs are non-selective and inhibit both COX-1 and COX-2 activity.

MCE offers a unique collection of 622 non-steroidal compounds with identified anti-inflammatory activity. MCE non-steroidal anti-inflammatory library is a useful tool for the study of anti-inflammatory drugs and pharmacology.

With the aging population and increasing competitive pressures, neurodegenerative diseases of the central nervous system (CNS) have become a serious medical challenge in modern society, including Parkinson's disease, Alzheimer's disease, brain tumors, and multiple sclerosis. However, the success rate of CNS drug development remains remarkably low, primarily due to the blood-brain barrier (BBB). The blood-brain barrier (BBB) is a semipermeable barrier structure that surrounds the microvasculature of the CNS. In capillaries, the wedged endothelial cells are tightly packed and wedge-shaped, lining the interior of the vessels to form extensive tight junctions. Along with a range of receptors, transporters, efflux pumps, and other cellular components, this barrier regulates the entry and exit of molecules between the bloodstream and the brain. The intact BBB blocks the passage of most blood-borne substances into the brain, preventing nearly 100% of large-molecule drugs and over 98% of small-molecule drugs from entering. Compared to non-CNS drugs, physicochemical properties such as hydrogen bonds, lipophilicity, and molecular weight significantly influence a compound's ability to cross the BBB. Using artificial intelligence (AI) algorithms to predict BBB permeability, a predicted value greater than 0.75 indicates that the compound has strong potential to cross the BBB, providing a promising starting point for CNS drug discovery.

Antibiotics are types of antimicrobial products used for the treatment and prevention of bacterial infections. Antibiotics can kill or inhibit bacterial growth. Although the target of an antibiotic is bacteria, some antibiotics also attack fungi and protozoans. However, antibiotics rarely have an effect on viruses. The major mechanism underlying antibiotics is the inhibition or regulation of enzymes involved in cell wall biosynthesis, nucleic acid metabolism and repair, protein synthesis, or disruption of membrane structure. Many of these cellular functions targeted by antibiotics are most active in multiplying cells. Since there is often overlap in these functions between prokaryotic bacterial cells and eukaryotic mammalian cells, it is not surprising that some antibiotics have also been found to be useful as anticancer agents.

MCE supplies a unique collection of 739 antibiotics, including penicillins, cephalosporins, tetracyclines, macrolides, etc. MCE Antibiotics Library is a useful tool for anti-bacterial or anti-cancer drugs discovery.

Mitochondria plays an important role in many vital processes in cells, including energy production, fatty-acid oxidation and the Tricarboxylic Acid (TCA) cycle, calcium signaling, permeability transition, apoptosis and heat production. At present, it is recognized that many diseases are associated with impaired mitochondrial function, such as increased accumulation of ROS and decreased OXPHOS and ATP production. Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases, etc. Some small molecule drugs or biologics can act on mitochondria through various pathways, including ETC inhibition, OXPHOS uncoupling, mitochondrial Ca²⁺ modulation, and control of oxidative stress via decrease or increase of mitochondrial ROS accumulation.

MCE supplies a unique collection of 869 mitochondria-targeted compound that mainly targeting Mitochondrial Metabolism, ATP Synthase, Mitophagy, Reactive Oxygen Species, etc. MCE Mitochondria-Targeted Compound Library is a useful tool for mitochondria-targeted drug discovery and related research.

Since ancient times, promoting blood circulation for removing blood stasis (PBCRBS) has been one of the most popular research contents in the area of traditional Chinese medicine (TCM) and integrated medicine. Rhizoma, Persicae Semen, Carthami Flos, Curcumae Longae Rhizoma and so on are common TCM with PBCRBS characteristic. Studies have shown that the mechanism of action of PBCRBS TCM is to promote blood circulation (improving cardiovascular and cerebrovascular functions, physical and chemical properties of blood, platelet and coagulation system and other physiological functions) and remove blood stasis (anti-myocardial ischemia, cerebral ischemia, inhibition of platelet aggregation, anti-coagulation, anti-thrombosis, etc.). Not only that, PBCRBS TCM has anti-infection, inhibit inflammation, regulate immune function, inhibit immune response, inhibit abnormal tissue proliferation and other functions. Therefore, PBCRBS TCM has high research value in all- field disease research fields.

MCE can supply 1,023 monomer component from more than a hundred sources of PBCRBS TCM, which can be used in TCM studies, drug development and mechanism-based studies.

The PI3K/Akt/mTOR pathway controls many cellular processes that are important for the formation and progression of cancer, including apoptosis, transcription, translation, metabolism, angiogenesis, and cell cycle progression. Every major node of this signaling network is activated in a wide range of human tumors. Mechanisms for the pathway activation include activation of receptor tyrosine kinases (RTKs) upstream of PI3K, mutation or amplification of PIK3CA encoding p110α catalytic subunit of PI3K, mutation or loss of PTEN tumor suppressor gene, and mutation or amplification of Akt1. Once the pathway is activated, signaling through Akt can stimulate a series of substrates including mTOR which is involved in protein synthesis. Thus, inhibition of this pathway is an attractive concept for cancer prevention and/or therapy. Currently some mTOR inhibitors are approved for several indications, and there are several novel PI3K/Akt/mTOR inhibitors in clinical trials.

MCE owns a unique collection of 842 compounds that can be used for PI3K/Akt/mTOR pathway research. PI3K/Akt/mTOR Compound Library also acts as a useful tool for anti-cancer drug discovery.

Ion channels are key proteins on the cell membrane that regulate the flow of ions across membranes. They participate in nearly all physiological processes, including nerve conduction, muscle contraction, heart rhythm, and pain perception. Abnormalities in their function can lead to various serious diseases such as arrhythmia, epilepsy, hypertension, neuropathic pain, and cancer. Therefore, ion channels are highly valuable drug targets—over 15% of approved drugs target ion channels currently, demonstrating their irreplaceable therapeutic value in cardiovascular, neurological, and analgesic fields.

MCE has collected a library of over 5,000 reported ion channel-related bioactive compounds targeting major sites such as Na+ channels, K+ channels, Ca2+ channels, GABA receptors, iGluRs, and others. Using AI models, these compounds are characterized through both 2D representations (molecular fingerprints, pharmacophores) and 3D representations (3D conformation) to screen for a collection of lead-like compounds highly similar to known active molecules. Additionally, an hERG channel prediction algorithm integrating XGB and ISE mapping strategy is employed to assess and exclude potential cardiotoxicity in the library.. This step significantly reduces safety risks in subsequent screenings, particularly for ion channel drug development related to cardiovascular systems (e.g., Nav1.5, Cav1.2), effectively minimizing failures due to hERG inhibition and serving as a valuable tool for ion channel drug screening.